DESCRIPTION: Progress made in recent years has greatly improved the understanding of the molecular mechanisms of retinoid action and now allows the design of retinoids which are highly selective, more potent than natural compounds, and also promise to have fewer side effects. In this proposal, lung cancer cells will be studied as a model system with a series of novel retinoids that have shown promising anti-cancer activities. The applicant will compare the activity of his novel retinoids to retinoic acid in a series of different lung cancer cell lines, including non-small cell and small cell lung cancer cells, and will analyze the molecular mechanisms underlying the enhanced anti-cancer activities of the retinoids. As it is unlikely that a single agent can be identified that specifically cures lung cancer, the applicant will also examine cooperativity between his highly active retinoids and other agents including vitamin D3 (VD) and interferons (IFNs). These investigations are designed to provide fundamental data on the molecular mechanisms of action related to inhibition of lung cancer cell growth.